Genetic heterogeneity: Challenges, impacts, and methods through an associative lens.
Genet Epidemiol
; 46(8): 555-571, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-35924480
ABSTRACT
Genetic heterogeneity describes the occurrence of the same or similar phenotypes through different genetic mechanisms in different individuals. Robustly characterizing and accounting for genetic heterogeneity is crucial to pursuing the goals of precision medicine, for discovering novel disease biomarkers, and for identifying targets for treatments. Failure to account for genetic heterogeneity may lead to missed associations and incorrect inferences. Thus, it is critical to review the impact of genetic heterogeneity on the design and analysis of population level genetic studies, aspects that are often overlooked in the literature. In this review, we first contextualize our approach to genetic heterogeneity by proposing a high-level categorization of heterogeneity into "feature," "outcome," and "associative" heterogeneity, drawing on perspectives from epidemiology and machine learning to illustrate distinctions between them. We highlight the unique nature of genetic heterogeneity as a heterogeneous pattern of association that warrants specific methodological considerations. We then focus on the challenges that preclude effective detection and characterization of genetic heterogeneity across a variety of epidemiological contexts. Finally, we discuss systems heterogeneity as an integrated approach to using genetic and other high-dimensional multi-omic data in complex disease research.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Heterogeneidade Genética
/
Medicina de Precisão
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Genet Epidemiol
Assunto da revista:
EPIDEMIOLOGIA
/
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos